tbuckley/cabot-search huggingface dataset:
Abstract 11652: What is the Relative Risk for Elevated Liver Function Tests of Single and Combined Statin and Alcohol Use and Implications for Management?
Authors: Benjamin D Horne, Viet T Le, Heidi T May, Stacey Knight, Tami L Bair, Joseph B Muhlestein, Kirk U Knowlton, Jeffrey L Anderson
Journal: Circulation (2022)

Introduction: Statins play a critical role in primary and secondary ASCVD prevention. Although uncommon, myalgias and abnormal liver function tests (LFTs) may limit statin use. Alcohol consumption also is a common cause of LFT elevations. It is unknown whether or to what extent concurrent alcohol and statin use may alter elevated LFT risk and impact management. Methods: Patients (pts) enrolled in the Intermountain INSPIRE registry who completed a health questionnaire for alcohol and other socioeconomic, dietary, and physical activity data were studied. Demographics, anthropometrics, cardiac risk factors, comorbidities, medication use, and laboratory results were obtained from electronic health records. Associations of alcohol and statin use with high ALT (females, &gt;40 U/L; males, &gt;55 U/L) were tested. Alcohol categories were: non-drinkers (ND; n=2797), moderate drinkers (MD; ≤7 drinks/week, n=980), and heavy drinkers (HD; &gt;7 drinks/week, n=164). Results: High ALT was found in 18.9%, 12.6%, and 10.5% of HD, MD, and ND respectively (p=0.002) and in 11.3% of both statin (n=2154) and non-statin users (n=1787) (p=0.97). After adjustment, HD vs. ND had OR=2.19 (CI: 1.44, 3.33; p&lt;0.001), and MD vs ND had OR=1.09 (CI: 0.86, 1.37; p=0.49). Pts not on statins had high ALT in 15.4% of HD (OR=1.47, CI: 0.73, 2.95; p=0.28) and 12.0% of MD (OR=1.10, CI: 0.79, 1.54; p=0.57) compared to 11.0% of ND. In parallel, pts on statins had high ALT in 21.2% of HD (OR=2.58, 95% CI: 1.52, 4.36; p&lt;0.001) and 13.0% of MD (OR=1.16, CI: 0.85, 1.59; p=0.34) vs. 10.2% of ND. Despite these trends, no formal interaction was found between statin use with HD (p-interaction=0.27) or with MD (p-interaction=0.43). Results for high AST (&gt;40 U/L) and low ALP (&lt;40 U/L) were similar to the ALT findings. Conclusions: In this prospective database, statin use was not associated with abnormal LFT findings, whereas risk was higher with increasing alcohol consumption. Concurrent statin and alcohol use was associated with a modestly elevated risk of abnormal LFT, but the interaction was not significant. Reducing alcohol consumption rather than reducing or discontinuing statins may reverse abnormal LFT while preserving the preventive benefit of statins. This hypothesis deserves further prospective testing.
Abstract 11871: Hypoglossal Nerve Stimulation as a Treatment for Sleep Apnea Does Not Lower Blood Pressure
Authors: Nathaniel Hitt, Adam Hoffmann, Sagar Patel, DENISA HAGAU
Journal: Circulation (2022)

Introduction: Obstructive sleep apnea (OSA) effects up to 30% of men and 15% of women in North America. Untreated, OSA is associated with the development of hypertension, heart failure, coronary artery disease, cardiac arrhythmia, and stroke. Treatment reduces these risks. The American Academy of Sleep Medicine outlines the first line treatment of OSA as continuous positive airway pressure (CPAP). However, many patients are unable to tolerate CPAP. One of the newest therapies approved in 2014 is implantation of a hypoglossal nerve stimulator (HNS) which functions by stimulating the tongue protrudor muscles to reduce upper airway obstruction. However, there is minimal research investigating HNS's effects on comorbidities. Currently there are two published studies showing improved blood pressure control and heart rate variability, but each study only included 46 patients. Several factors warrant a comparison including the lack of data, procedural risks, and procedural cost; especially, when considering the proven efficacy and low cost of CPAP. We present a retrospective analysis of blood pressure after HNS implantation. Hypothesis: We hypothesize that HNS implantation will improve blood pressure control. Methods: All cases of HNS implantation at MercyOne North Iowa Mason City, Iowa were retrospectively reviewed. Each case was manually reviewed for pre- and post-surgery blood pressure, heart failure exacerbations, arrhythmia, hemoglobin A1c, stroke, and acute coronary syndrome. Results: Fifty-nine patients had a mean change in blood pressure of +1.76 systolic and +0.76 diastolic with a standard error of 2.10 and 1.29 respectively. The mean follow-up time was 5.7 months after the fine-tuning sleep titration study. Five patients needed one less blood pressure medication and 6 patients needed one more. Preliminary regression analysis does not support gender, age, apnea-hypopnea index, or body mass index being predictive of change in blood pressure with HNS implantation. There was no statistically significant effect on other comorbidities. Conclusion: This study showed no clinically significant change in blood pressure after HNS implantation. Limitations include the small sample size and only one follow-up blood pressure.
Abstract 11716: A Systematic Review on Cardiac Papillary Fibroelastoma Presenting With Cerebrovascular Events
Authors: Gagan Neupane, Raksha Sharma
Journal: Circulation (2022)

Introduction: Cardiac papillary fibroelastomas (CPF) are rare, benign endocardial tumors with embolic complications like cerebrovascular events. The objective of this systematic review is to identify the clinical profile, diagnostic approach, tumor characteristics, and treatment modalities of patients with CPF presenting with stroke or TIA. Methods: We performed a systematic review using PUBMED and EMBASE databases involving all the published case reports and case series of CPF with TIA or stroke as presentation until April 2022. Viewpoints, editorials, and review articles were excluded. Results: A total of 161 cases were identified from 133 case reports and 11 case series. The mean age was 54.8 ± 15.6 years with 53.4% females. The proportion of patients with TIA and stroke was 32.3% and 67.8% respectively. Neuroimaging demonstrated the involvement of multiple sites (36.6%) and middle cerebral artery territory (35.6%) as major sites of stroke. The primary imaging tool for the diagnosis of CPF was echocardiogram. The size of the tumor varied from 2 to 47 mm (mean 11.8 ± 7.1). Left-sided valves were the most common location of the tumor (73.2%). Mitral valve was the most common valve involved (38.9%) with the anterior leaflet being the more common site (61.3%). The aortic valve was involved in 32.5% with non-coronary cusp being the more common site (37.5%). About 10.6% of cases were missed by TTE (mean size of valvular tumors missed by TTE was 5.6 ± 1.9 mm). Most of the tumors (91.4%) showed independent mobility. Surgical excision was performed in 89.5% cases with histopathological confirmation. Medical management prior to surgery included antiplatelets (87.9%) and anticoagulation (12.1%). Simple excision, excision with valve repair and excision with valve replacement were done in 66.7%, 16.7% and 16.7% respectively. Most patients (97.8%) had uneventful post-operative course. Conclusions: CPFs are potential differential diagnosis for cryptogenic stroke. TEE serves as a better diagnostic modality for cardiac workup of cryptogenic stroke if the initial TTE is negative. While the consensus for CPF management remains controversial, the results of our study support surgical management as the primary approach for left-sided tumors presenting as stroke/TIA.
Abstract 11669: Quantitative and Automated Breast Arterial Calcification Score is Associated With Traditional Cardiovascular Risk Factors
Authors: Tara S Allen, Quan M Bui, Alexandra V Sykes, Nora Belrose, Nitesh Nerlekar, Richard Mantey, Junhao Wang, Mohammad Eghtedari, Lori B Daniels
Journal: Circulation (2022)

Introduction: Breast arterial calcification (BAC) is gaining acceptance as a CVD risk factor (RF), though overlap with traditional RFs remains unclear. We tested the hypothesis that BAC, assessed via the Bradley score, is associated with CVD RFs. Methods: We analyzed baseline cross-sectional data from 16,217 women who underwent screening digital mammography between 2008-2016 at a single center. BAC was quantified using an algorithm from a trained, deep neural network (CureMetrix), resulting in an automated and continuous Bradley score; &gt;10 was considered BAC positive. CVD RFs were obtained via medical records. We calculated odds ratios (OR) for RFs per Bradley score quartile and created distribution plots. Results: At baseline (mean age 55 ± 11 yrs; 70% White, 45% Black, 25% other), 8% had diabetes, 30% hypertension, 30% hyperlipidemia, and 5% smoked; 22% and 6% took lipid-lowering and anticoagulant medication, respectively. There were 1,904 women (13%) with BAC (median Bradley score 42). BAC prevalence increased with age, and those in the highest quartile of the Bradley score, compared to lowest, were significantly more likely to have hypertension (OR 4.1, 95% CI 3.3-5.0; p&lt;0.001), diabetes (OR 2.8, 95% CI 2.2-3.6; p&lt;0.001), and hyperlipidemia (OR 2.4, 95% CI 2.0-3.0; p&lt;0.001) ( Figure). Additionally, 492 women (7%) with zero traditional RFs had BAC ( Table ). Conclusions: BAC prevalence on mammography is robustly associated with traditional CVD RFs, however BAC was present in 7% of women without RFs. Future studies are needed to determine the significance of BAC among women without RFs, as it may provide insight and opportunity for prevention before traditional CVD RFs develop.
Abstract 11706: Association of Left Atrial Function With Incident Chronic Kidney Disease: Atherosclerosis Risk in Communities (ARIC) Study
Authors: Jorge L Reyes, Abayomi Oyenuga, ANNE EATON, Wendy Wang, Romil Parikh, Riccardo M Inciardi, Alvaro Alonso, Pamela L Lutsey, Elsayed Z Soliman, Charles Herzog, Junichi Ishigami, Kuni Matsushita, Josef Coresh, Amil M Shah, Scott Solomon, Lin Y Chen
Journal: Circulation (2022)

Introduction: Echocardiographic measures of left ventricular (LV) structure and function are associated with incident chronic kidney disease (CKD). Reduced left atrial (LA) function is an emerging novel risk factor for cardiovascular disease but its association with incident CKD is unknown. Hypothesis: Lower LA function is independently associated with incident CKD in older adults in the ARIC study, a prospective community-based cohort. Methods: We included ARIC participants without prevalent CKD (as defined by eGFR&lt;60ml/min/1.73m 2 ) who underwent echocardiographic exam at visit 5 (2011-13). LA function measures included LA reservoir strain, contractile strain, and conduit strain. Incident CKD was defined as a composite outcome of &gt;25% decline to eGFR &lt;60 mL/min/1.73m 2 , hospitalization with CKD diagnosis, or incident end-stage kidney disease through 2017. Cox proportional hazards model was used. Results: Among the 3,970 participants (mean [SD] age, 75 [5] years; 58% women; 20.9% Black individuals), 382 cases of incident CKD were ascertained over a median follow-up of 5.5 years. Lower LA reservoir and contractile strain were significantly associated with higher risk of CKD (HR [95% CI] lowest vs highest quintile: 2.76 [1.91-3.98], and 2.56 [1.79-3.65], respectively) (Table). The associations remained significant after accounting for other major echocardiographic parameters (model 2) including left atrial volume index (model 3). LA conduit strain was not significantly associated with CKD. Conclusions: Lower LA function is significantly associated with incident CKD, independent of CKD risk factors, LV size and function, and LA size. These findings indicate that impaired LA function is a novel predictor marker for CKD.
Abstract 11502: Exercise Stress Testing for Arrhythmic Mitral Valve Prolapse
Authors: Forrest N Gamble, Kelly E Arps, Sean Pokorney, Albert Sun
Journal: Circulation (2022)

Background - Mitral valve prolapse (MVP) is a common valvular abnormality found in approximately 2.4% of the population. Whereas the majority of cases are benign, an increasingly recognized sequela of MVP is sudden cardiac death (SCD), but triggers and risk factors for SCD are not well-defined. It is theorized that increased stretch on the papillary muscles due to MVP leads to papillary muscle fibrosis and cellular changes of local conduction properties, increasing the risk of ventricular arrhythmias and SCD. Hypothesis - We hypothesized that patients with MVP and SCD would have increased ventricular arrhythmias and ECG changes compared to MVP controls during exercise stress testing. Methods - The study population was generated from the Duke Epic. Patients were included if they had guideline-based diagnosis of MVP on echocardiogram or cardiac magnetic resonance imaging. Increase in ventricular arrhythmias during exercise was defined as &gt;/= 10 PVCs per minute, multifocal PVCs, or &gt;/= 2 PVCs in a row. Results- A total 2,513 patients with MVP were screened. 18 patients with SCD. Patients with SCD were younger [(47.22 +/- 12.2 ) vs. (58.0 +/- 18.7), p=0.02], more likely to be female (89.9% vs 64%, p=0.04) and had increased rate of bileaflet prolapse (72% vs. 40%, p=0.01) compared to controls. Patients with sudden cardiac death had either dynamic T wave changes or increased ventricular arrhythmias with stress testing versus controls [12/18 (66.7%) vs 17/75 (22.6%), p &lt;0.001]. Conclusions - Increased ventricular arrhythmias on exercise stress testing is associated with sudden cardiac death in mitral valve prolapse and may prove a useful tool for further risk stratification.
Abstract 11586: Therapeutic Potential of Alpha Lipoic Acid in a Rat Model of Superimposed Preeclampsia: Effect on Maternal Signs, Placental Development and Fetal Growth
Authors: Gabriela Barrientos, Claudio A Incardona, Graciela Giardina, Ana M Uceda, Ma Alejandra Sgariglia, Monica Galleano, Silvia I Garcia
Journal: Circulation (2022)

Introduction: Superimposed preeclampsia (SPE) occurs in 25-40% of pregnant women affected by chronic hypertension and is associated with adverse maternal and neonatal outcomes. In previous studies, we have demonstrated that pregnant Stroke-prone Spontaneously Hypertensive Rat represent a spontaneous SPE model, characterized by defective trophoblast invasion and placental oxidative stress, asymmetric fetal growth restriction and worsening maternal hypertension with renal dysfunction towards term. Here, we sought to evaluate the therapeutic potential of alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy in this model. Methods: Congenic timed breedings were established using SHRSP and Wistar Kyoto (WKY) females (10-12 weeks old, 200-250 g body weight, N = 10 animals/day analyzed). Upon vaginal plug detection (gestation day (GD)1), dams were assigned to two groups: ALA treatment, injected 25mg/kg body weight ALA i.p. on GD1, GD8 and GD12 and controls, receiving saline following the same protocol. Systolic blood pressure (SBP) profiles throughout pregnancy were recorded using a noninvasive volume pressure recording device. On GD20, animals were euthanized and fetoplacental specimens isolated for morphological and molecular analyzes. Statistical analysis was run on GraphPad Prism v 8.0, using 2 way ANOVA. Statistical significance was set at p˂ 0.05. Results: Treatment with ALA prevented the pregnancy-dependent SBP increase typical of the SHRSP model (SBP GD14 SHRSP: 169.3±2.1 mmHg vs. SHRSP+ALA: 146.1±3.4, p˂0.001). Furthermore, fetuses carried by ALA-treated SHRSP displayed increased weights (SHRSP: 1.75±0.05g vs. SHRSP+ALA: 1.99±0.01g, p˂0.05) and decreased cephalization indexes on GD20, indicating an improvement in the asymmetric growth restriction pattern. Treated dams also presented increased numbers of glycogen trophoblasts (PAS + cells) in the junctional zone and an enhanced vessel density on Isolectin B4 + staining, suggesting an improved placental function. Conclusions: ALA administration during early pregnancy in the SHRSP model ameliorated maternal signs and improved placental function and fetal growth, emerging as a novel therapeutic intervention in pregnancies affected by chronic hypertension
Functional and organic tic disorders . . . and other stories
Journal: BMJ (2023)

A few years ago, a German YouTube channel, Gewitter im Kopf (thunderstorm in the head), created by a young man with Tourette's syndrome was blamed for provoking a mass sociogenic illness when numerous teenagers presented with tics and other behaviours characteristic of Tourette's syndrome.Distinguishing between functional and organic tic disorders isn't straightforward.When eight experts in the diagnosis and management of tics were asked to study videos of 24 adults with primary tics, functional tics, or both, inter-rater agreement was only moderate (
Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study
Authors: Zhaozhong Zhu, Robert J. Freishtat, Brennan Harmon, Andrea Hahn, Stephen J. Teach, Marcos Pérez-Losada, Kohei Hasegawa, Carlos A. Camargo
Journal: European Respiratory Journal (2023)

Background Severe bronchiolitis ( i.e. bronchiolitis requiring hospitalisation) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway miRNAs during severe bronchiolitis and the risk of developing asthma. Methods In a 17-centre prospective cohort study of infants with severe bronchiolitis, we sequenced their nasal microRNA at hospitalisation. First, we identified differentially expressed microRNAs (DEmiRNAs) associated with the risk of developing asthma by age 6 years. Second, we characterised the DEmiRNAs based on their association with asthma-related clinical features, and expression level by tissue and cell types. Third, we conducted pathway and network analyses by integrating DEmiRNAs and their mRNA targets. Finally, we investigated the association of DEmiRNAs and nasal cytokines. Results In 575 infants (median age 3 months), we identified 23 DEmiRNAs associated with asthma development ( e.g. hsa-miR-29a-3p; false discovery rate (FDR) &lt;0.10), particularly in infants with respiratory syncytial virus infection (FDR for the interaction &lt;0.05). These DEmiRNAs were associated with 16 asthma-related clinical features (FDR &lt;0.05), e.g. infant eczema and corticosteroid use during hospitalisation. In addition, these DEmiRNAs were highly expressed in lung tissue and immune cells ( e.g. T-helper cells, neutrophils). Third, DEmiRNAs were negatively correlated with their mRNA targets ( e.g. hsa-miR-324-3p/ IL13 ), which were enriched in asthma-related pathways (FDR &lt;0.05), e.g. toll-like receptor, PI3K-Akt and FcɛR signalling pathways, and validated by cytokine data. Conclusion In a multicentre cohort of infants with severe bronchiolitis, we identified nasal miRNAs during illness that were associated with major asthma-related clinical features, immune response, and risk of asthma development.
Abstract 10355: Allostatic Load and Cardiovascular Outcomes in Males With Prostate Cancer
Authors: Nickolas Stabellini, Jennifer Cullen, Justin Moore, Lifen Cao, Neal L Weintraub, Ryan A Harris, Xiaoling Wang, Biplab Datta, Jorge Garcia, John Shanahan, Nelson Hamerschlak, Kristin Waite, Martha Terris, Nathanael Fillmore, Alberto Montero, Jill Barnholtz-Sloan, Avirup Guha
Journal: Circulation (2022)

Introduction: Prostate cancer (PC) is the leading type of newly diagnosed cancer in males. Cardiovascular disease (CVD) is the leading cause of death in men with PC. Accumulated stress, which is triggered by multiple environmental factors and life events, plays an important role in CVD development. The cumulative burden of chronic stress and life events can be measured using allostatic load (AL). Hypothesis: We hypothesize that AL is associated with the development of major cardiac events (MACE) after the diagnosis of PC. Methods: Data were obtained from a Cleveland area integrated health care systems informatics platform. The initial cohort included males ≥18 years diagnosed with PC between 2005 and 2019. AL was modeled as an ordinal variable from 0 to 11. Fine and Gray competing risk regression model accounting for the competing risk of all-cause mortality were used to calculate the impact of pre-cancer diagnosis AL and post-diagnosis AL in 2-year major cardiac events (MACEs). The effect of AL variation over time on MACEs development was calculated via the piecewise Cox Regression model where the time periods considered were before PC diagnosis, 2 months after, 6 months after and 1-year after PC diagnosis. Results: We analyzed 5,261 (19,840 person-years) PC adenocarcinoma patients, of which 6.6% (N=347) had a 2-year MACE. For every 1 point increase in AL before PC diagnosis and within 60 days after PC diagnosis the risk of MACE increased 25% (adjusted Hazards Ratio [aHR] =1.25, 95% Confidence Interval [CI] = 1.18-1.33), and 27% (aHR=1.27; 95% CI = 1.20-1.35), respectively. Using AL as a time varying exposure, the risk of MACE increased 19% (aHR=1.19, 95% CI 1.11-1.27), 22% (aHR=1.22, 95% CI 1.14-1.33), 28% (aHR=1.28, 95% CI 1.23-1.33), and 31% (aHR=1.31, 95% CI 1.27-1.35) for every 1 point increase in AL before PC diagnosis, 2 months after, 6 months after and 1-year after PC diagnosis, respectively. Conclusion: AL and its variation over time are associated with MACE in PC patients, suggesting a role of a biological measure of stress as a marker of CVD risk among men with PC. Preventive measures to minimize AL may require collaboration between cancer control and cardio-oncology.
Abstract 10360: Polygenic Risk Score, Rare Monogenic Variants, and Family History Have Independent and Additive Effects on the Risk of Coronary Heart Disease
Authors: Seyedmohammad Saadatagah, Marwan Hamed, Alexandra Miller, Hana Bangash, Scott Nigbur, Arailym Kamzabek, Kristjan Norland, Matt Kosel, Daniel Schaid, Iftikhar J Kullo
Journal: Circulation (2022)

Introduction. We assessed the effects of a polygenic risk score (PRS), monogenic variants (Mono + ), and family history (FamHx) on the risk of coronary heart disease (CHD) and whether incorporating a PRS into the Pooled Cohort Equations (PCE) improves risk prediction. Method. In 199,997 UK Biobank participants, we calculated a PRS CHD (metaGRS, based on ~1.6 million single nucleotide variants), identified individuals with monogenic etiology (presence of a pathogenic variant in LDLR , APOB , or PCSK9 ), and ascertained family history of CHD (CHD in a first-degree relative). Odds of CHD (myocardial infarction/ coronary revascularization/ cardiovascular death) associated with PRS CHD , Mono + , and FamHx at age 55 were computed using logistic regression analyses adjusted for age, sex, and first 4 principal components of ancestry. We combined PRS CHD and PCE into an integrated score (IS) and assessed net reclassification using an actionable risk threshold of 7.5%. Results. The odds ratio (OR) for CHD in the top 5 th percentile of PRS CHD (PRS P95 ), Mono + , and FamHx were 3.37 (2.98 - 3.81), 2.68 (1.67 - 4.07), and 1.61 (1.47 - 1.76), respectively (all p&lt;0.001). These effects were independent and similar in different subgroups. ( Figure 1-A ) Compared to PRS Q2-4 Mono - (3 middle quintiles of PRS CHD and no monogenic variants), the OR for CHD ranged from 1.73 (0.28 - 5.48, p = 0.446) in PRS Q1 Mono + to 5.10 (2.14 - 10.24, p &lt;0.001) in PRS Q5 Mono + . A similar pattern was seen for other combinations, indicating additive effects ( Figure 1-B ). Incorporating PRS CHD into PCE resulted in a net reclassification improvement of 4.56%. Compared to those with high PCE and low IS, the hazard ratio for CHD in those with low PCE and high IS was 1.48 (1.34 - 1.64, p &lt;0.001). Conclusion. The CHD risk associated with PRS CHD , monogenic variants, and family history is independent and additive. Combining PRS CHD and PCE improved risk prediction, that could improve further by adding monogenic variants and family history.